One of the consistent cardiovascular changes associated with aging is the decrease in maximal heart rate to exercise. In the past, we have explored the mechanism for this decrease by examining b-adrenoceptor change with aging. Using adipocytes as a prototype cell that has both b1- and b2- adrenoceptors, we could not identify any changes in b-adrenoceptor sensitivity with aging. We then tested the hypothesis that excessive adenosine release or sensitivity was the abnormality with aging that results in the decrease in maximal heart rate. Using theophylline to block adenosine receptors, we were unable to demonstrate that adenosine had a major role in this down-regulated response in the elderly. This present study explored the role of L-type calcium channels, and the effect of blocking them with diltiazem, in the cardiovascular response to maximal exercise with aging. The hypothesis was that if aging is associated with a down-regulated L-type calcium channel, or the inability to keep the calcium channel in an open state, then elderly subjects would have less of a heart rate effect during exercise with diltiazem administration than the young group. Thus, a group of healthy young and old men (n+8 in each) were subjected to maximal exercise test twice, once with placebo and once after diltiazem infusion. Our data were corrected to plasma concentration of diltiazm. Indeed, we found that the young group had a greater decrease in maximal heart rate to exercise than the old group (young:185 +/- with placebo, 178 +/- with diltiazem; old 150 +/- with placebo, 148 +/- with diiltiazm). When we correlated the plasma concentration of diltiazem at the end of exercise with the change in maximal heart rate (placebo- diltiazem) in the two age groups, the young group demonstrated a significant correlation (p+0.05) With increasing change in heart rat to increasing diltiazem concentration, while the old group had no such correlation. These data suggest that one explanation for the reduced maximal heart rate response with aging may very well be secondary to abnormal calcium channels in pacemaker cells resulting in slower depolarization to stimuli.